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An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available OTC (over-the-counter).

Types

There are two types of antifungals: local and systemic. Local antifungals are usually administered topically or vaginally, depending on the condition being treated. Systemic antifungals are administered orally or intravenously.

Of the clinically employed azole antifungals, only a handful are used systemically.[1] These include ketoconazole, itraconazole, fluconazole, fosfluconazole, voriconazole, posaconazole, and isavuconazole.[1][2] Examples of non-azole systemic antifungals include griseofulvin and terbinafine.

Classes

Polyenes

A polyene is a molecule with multiple conjugated double bonds. A polyene antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring opposite the conjugated system. This makes polyene antifungals amphiphilic. The polyene antimycotics bind with sterols in the fungal cell membrane, principally ergosterol. This changes the transition temperature (Tg) of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. (In ordinary circumstances membrane sterols increase the packing of the phospholipid bilayer making the plasma membrane more dense.) As a result, the cell's contents including monovalent ions (K+, Na+, H+, and Cl), small organic molecules leak and this is regarded one of the primary ways a cell dies.[3] Animal cells contain cholesterol instead of ergosterol and so they are much less susceptible. However, at therapeutic doses, some amphotericin B may bind to animal membrane cholesterol, increasing the risk of human toxicity. Amphotericin B is nephrotoxic when given intravenously. As a polyene's hydrophobic chain is shortened, its sterol binding activity is increased. Therefore, further reduction of the hydrophobic chain may result in it binding to cholesterol, making it toxic to animals.

Azoles

Azoles inhibit conversion of lanosterol to ergosterol by inhibition of azole antifungals, only a handful are used systemically.[1] These include ketoconazole, itraconazole, fluconazole, fosfluconazole, voriconazole, posaconazole, and isavuconazole.[1][2] Examples of non-azole systemic antifungals include griseofulvin and terbinafine.

Classes

Polyenes

A polyene is a molecule with multiple conjugated double bonds. A polyene antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring opposite the conjugated system. This makes polyene antifungals amphiphilic. The polyene antimycotics bind with sterols in the fungal cell membrane, princi

Of the clinically employed azole antifungals, only a handful are used systemically.[1] These include ketoconazole, itraconazole, fluconazole, fosfluconazole, voriconazole, posaconazole, and isavuconazole.[1][2] Examples of non-azole systemic antifungals include griseofulvin and terbinafine.

A polyene is a molecule with multiple conjugated double bonds. A polyene antifungal is a macrocyclic polyene with a heavily hydroxylated region on the ring opposite the conjugated system. This makes polyene antifungals amphiphilic. The polyene antimycotics bind with sterols in the fungal cell membrane, principally ergosterol. This changes the transition temperature (Tg) of the cell membrane, thereby placing the membrane in a less fluid, more crystalline state. (In ordinary circumstances membrane sterols increase the packing of the phospholipid bilayer making the plasma membrane more dense.) As a result, the cell's contents including monovalent ions (K+, Na+, H+, and Cl), small organic molecules leak and this is regarded one of the primary ways a cell dies.[3] Animal cells contain cholesterol instead of ergosterol and so they are much less susceptible. However, at therapeutic doses, some amphotericin B may bind to animal membrane cholesterol, increasing the risk of human toxicity. Amphotericin B is nephrotoxic when given intravenously. As a polyene's hydrophobic chain is shortened, its sterol binding activity is increased. Therefore, further reduction of the hydrophobic chain may result in it binding to cholesterol, making it toxic to animals.

AzolesAzoles inhibit conversion of lanosterol to ergosterol by inhibition of lanosterol 14α-demethylase.[4]

Imidazoles

  • Bifonazole
  • Butoconazole
  • Clotrimazole
  • Econazole
  • Fenticonazole
  • Isoconazole
  • Ketoconazole
  • Luliconazole
  • Allylamines[5] inhibit squalene epoxidase, another enzyme required for ergosterol synthesis. Examples include amorolfin, butenafine, naftifine, and terbinafine.[6][7][8]

    Echinocandins

    Echinocandins inhibit the creation of glucan in the fungal cell wall by inhibiting 1,3-Beta-glucan synthase:

    Echinocandins are administered intravenously, particularly for the treatment of resistant Candida species.[9][10]

    Others

    • Aurones - have been shown to possess antifungal properties[11]
    • Benzoic acid – has antifungal properties, such as in Whitfield's ointment, Friar's Balsam, and Balsam of Peru.[12]
    • Ciclopirox – (ciclopirox olamine) – is a hydroxypyridone antifungal that interferes with active membrane transport, cell membrane integrity, and fungal respiratory processes. It is most useful against tinea versicolour.[13]
    • Flucytosine or 5-fluorocytosine – an antimetabolite pyrimidine analog [14]
    • Griseofulvin – binds to polymerized Echinocandins inhibit the creation of glucan in the fungal cell wall by inhibiting 1,3-Beta-glucan synthase:

      Echinocandins are administered intravenously, particularly for the treatment of r

      Echinocandins are administered intravenously, particularly for the treatment of resistant Candida species.[9][10]

      Others

      References

      1. ^ a b Benitez, Lydia L.; Carver, Peggy L. (2019). "Adverse Effects Associated with Long-Term Administration of Azole Antifungal Agents". Drugs. 79 (8): 833–853. doi:10.1007/s40265-019-01127-8. ISSN 0012-6667. PMID 31093949. S2CID 155093431.